Gene Structure of Human Mitochondrial Atp Synthase Gamma-Subunit - Tissue-Specificity Produced by Alternative Rna Splicing

  • Matsuda C
  • Endo H
  • Ohta S
 et al. 
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We completely sequenced the human gene for ATP synthase gamma-subunit, which was approximately 23 kilobases long and was composed of 10 exons. Exons 1 and 2 encoded the N-terminal presequence required for mitochondrial import, while exons 9 and 10 encoded the C-terminal portions of mature protein. Enzymatic amplification of human heart and liver cDNAs using the polymerase chain reaction revealed two mRNA transcripts that were predicted to encode two 30-kDa isoforms of the gamma-subunit, which differed by the addition of a single amino acid (Asp273) at the C terminus of the liver type isoform. These two mRNA transcripts of the heart (H) type and liver (L) type were generated by alternative splicing of an exon. The same alternative splicing event was observed in bovine tissue. In human tissues, the H type mRNA devoid of exon 9 was expressed specifically in the heart and skeletal muscle, which require rapid energy supply. The L type mRNA was expressed in the brain, liver, kidney etc. Both transcripts were expressed in the skin, intestine, stomach, and aorta. This tissue specificity of transcript heterogeneity suggests the distinct functional or regulatory roles of the gamma-subunit isoforms in the catalysis of ATP synthase. This is the first report on tissue-specific isoforms generated by alternative splicing in an energy transducing mitochondrial protein.

Author-supplied keywords

  • adenosine-triphosphate synthase
  • beta-subunit
  • binding protein
  • escherichia-coli
  • import precursor
  • molecular-cloning
  • muscle adp/atp translocator
  • nucleotide-sequence
  • promoter sequences
  • transcriptional activation

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  • C Matsuda

  • H Endo

  • S Ohta

  • Y Kagawa

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